Andersson Theresa N, Ekman Gunilla J, Grönlund Hans, Buentke Eva, Eriksson Tove L J, Scheynius Annika, Van Hage-Hamsten Marianne, Gafvelin Guro
Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska Institutet and University Hospital, Stockholm, Sweden.
Immunology. 2004 Oct;113(2):253-9. doi: 10.1111/j.1365-2567.2004.01943.x.
Allergen-specific immunotherapy is commonly performed with allergen extracts adsorbed to aluminium hydroxide (alum). The undesirable effects associated with the use of alum, including granuloma formation at the site of injection and stimulation of T helper 2 (Th2) cytokine production, has generated interest in alternative allergen carriers, one being carbohydrate-based particles (CBPs). Here, we have investigated the in vitro effects of the recombinant major cat allergen Fel d 1 (rFel d 1) coupled to CBPs (CBP-rFel d 1) on human monocyte-derived dendritic cells (MDDCs) obtained from healthy blood donors. A majority of the CD1a(+) MDDCs internalized fluorescein isothiocyanate-labelled CBP-rFel d 1, as demonstrated by flow cytometry and confocal laser-scanning microscopy. Furthermore, an up-regulation of the expression of the costimulatory molecule, CD86, on the MDDCs was induced by CBP-rFel d 1, but not by rFel d 1 or CBPs alone. Finally, three- and fourfold increases in the release of interleukin-8 and tumour necrosis factor-alpha, respectively, were observed when MDDCs were cultured in the presence of CBP-rFel d 1. Altogether, our results indicate that the use of CBPs as an allergen carrier and adjuvant is a promising candidate for the improvement of allergen-specific immunotherapy.
变应原特异性免疫疗法通常使用吸附于氢氧化铝(明矾)的变应原提取物来进行。与使用明矾相关的不良影响,包括注射部位形成肉芽肿以及刺激辅助性T细胞2(Th2)细胞因子的产生,引发了人们对替代变应原载体的兴趣,其中一种是基于碳水化合物的颗粒(CBP)。在此,我们研究了与CBP偶联的重组主要猫变应原Fel d 1(CBP-rFel d 1)对从健康献血者获得的人单核细胞衍生树突状细胞(MDDC)的体外作用。流式细胞术和共聚焦激光扫描显微镜显示,大多数CD1a(+) MDDC内化了异硫氰酸荧光素标记的CBP-rFel d 1。此外,CBP-rFel d 1可诱导MDDC上共刺激分子CD86表达上调,但单独的rFel d 1或CBP则无此作用。最后,当MDDC在CBP-rFel d 1存在下培养时,观察到白细胞介素-8和肿瘤坏死因子-α的释放分别增加了三倍和四倍。总之,我们的结果表明,使用CBP作为变应原载体和佐剂有望改善变应原特异性免疫疗法。